Hanna Romanowicz

Instytut Centrum Zdrowia Matki Polki, Łódź, Łódź Voivodeship, Poland

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Publications (24)37.02 Total impact

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    ABSTRACT: The variability, perceived in DNA repair genes, may be of clinical importance for evaluation of the risk of occurrence of a given type of cancer, its prophylactics and therapy. The aim of the present work was to evaluate associations between the risk of ovarian cancer and polymorphisms in the genes, encoding for two key proteins of homologous recombination: XRCC2 Arg188His (c. 563 G > A; rs3218536) and XRCC3 Thr241Met (c. 722 C > T; rs 861,539). The study consisted of 700 patients with ovarian cancer and 700 healthy subjects. Analysis of the gene polymorphisms was performed using PCR-RFLP (restriction length fragment polymorphism). We found a statistically significant increase of the 188His allele frequency (OR = 4.01; 95% CI = 3.40–4.72; p < .0001) of XRCC2 in ovarian cancer compared to healthy controls. There were no differences in the genotype and allele distributions and odds ratios of the XRCC3 Thr241Met polymorphism between patients and controls group. Association of these genetic polymorphisms with histological grading showed increased XRCC2 188Arg/His (OR = 33.0; 95% CI = 14.51–75.05; p < .0001) and 188His/His genotype (OR = 9.37; 95% CI = 4.79–18.32; p < .0001) and XRCC3 241Thr/Met (OR = 24.28; 95% CI = 12.38–47.61; p < .0001) and 241Met/Met genotype frequencies (OR = 17.00; 95% CI = 8.42–34.28; p < .0001) in grading 1 (G1) as well as 188His (OR = 2.78; 95% CI = 2.11–3.69; p < .0001) and 241Met allele overrepresentation (OR = 2.59; 95% CI = 2.08–3.22; p < .0001) in G1 ovarian patients. Finally, with clinical FIGO staging under evaluation, an increase in XRCC2 188His/His homozygote and 188Arg/His heterozygote frequencies in staging I (SI) and XRCC3 Thr/Met heterozygote frequencies in SI were observed. The obtained results indicate that XRCC2 Arg188His and XRCC3 Thr241Met polymorphisms may be positively associated with the incidence of ovarian carcinoma in the population of Polish women.
    No preview · Article · Jan 2016 · Experimental and Molecular Pathology
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    ABSTRACT: Aim. The aim of this study was to evaluate the role of the Lys751Gln (rs13181) ERCC2 gene polymorphism in clinical parameters and the risk for development of ovarian cancer. Material and Methods. The study consisted of 430 patients with ovarian cancer (mean age: 53.2 ± 10.11) and 430 healthy subjects (mean age: 50.31 ± 18.21). Analysis of the gene polymorphisms was performed using the PCR-based restriction fragment length polymorphism (PCR-RFLP). The odds ratios (ORs) and 95% confidence intervals (CIs) for each genotype and allele were calculated. Results. The results obtained indicate that the genotype Gln/Gln is associated with an increased risk of ovarian cancer (OR 5.01; 95% CI 3.37–7.43; p < 0. 0001 ). Association of Lys751Gln polymorphism with histological grading showed increased ERCC2 Gln/Gln (OR = 6.96; 95% CI 3.41–14.21; p < 0. 0001 ) genotype in grading 1 as well as Gln allele overrepresentation (OR = 4.98; 95% CI 3.37–7.40; p < 0. 0001 ) in G1 ovarian patients. Finally, with clinical FIGO staging under evaluation, an increase in ERCC2 Gln/Gln homozygote frequencies in staging I and Gln allele frequencies in SI were observed. Conclusion. On the basis of these results, we conclude that ERCC2 gene polymorphism Lys751Gln may be associated with an increased risk of ovarian carcinoma.
    Preview · Article · Nov 2015
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    ABSTRACT: Endometrial carcinoma (EC) is the most frequent malignant neoplasm of female genitals and the fourth most frequent malignant neoplasm in Polish women, after breast, colorectal and lung cancer. Despite intensive research, EC aetiology remains unknown. The variability, perceived in DNA repair genes, may be of clinical importance for evaluation of the risk of occurrence of a given type of cancer, its prophylactics and therapy. The aim of the study was to determine the relationship between gene polymorphism R156R (C to A, rs238406) of ERCC2 gene and modulation of the risk of endometrial cancer in Poland. Our research included 1360 patients with EC and 1320 healthy controls. The genotype analysis of ERCC2 gene polymorphism was performed using the PCR-based restriction fragment length polymorphism (PCR-RFLP). In the presented study, a relationship was identified between R156R polymorphism of the ERCC2 gene and the incidence of endometrial cancer. An association was observed between EC occurrence and the presence of A/A genotype (odds ratio (OR) 9.71, 95 % Cl 7.53-12.50, p < .0001). A tendency for an increased risk of endometrial cancer was detected with the occurrence of A allele of ERCC2 polymorphism (OR = 5.95, 95 % Cl 5.23-6.78, p < .0001). A relationship was confirmed between R156R polymorphism and endometrial cancer progression, assessed by histological grades. On the basis of these results, we conclude that ERCC2 gene polymorphism R156R may be associated with an increased risk of endometrial cancer.
    No preview · Article · Sep 2015 · Tumor Biology
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    ABSTRACT: The aim of this study was to determine single nucleotide polymorphisms in hOGG1 (Ser326Cys (rs13181)) and XRCC1 (Arg194Trp (rs1799782)) genes, respectively, and to identify the correlation between them and the overall risk, grading and staging of ovarian cancer in Polish women. Our study comprised 720 patients diagnosed with ovarian cancer and 720 healthy controls. The genotype analysis of hOGG1 and XRCC1 polymorphisms was performed using polymerase chain reaction (PCR)-based restriction fragment length polymorphism (PCR-RFLP). Odds ratios (OR) and 95 % confidence intervals (CI) for each genotype and allele were calculated. Results revealed an association between hOGG1 Ser326Cys polymorphism and the incidence of ovarian cancer. Variant Cys allele of hOGG1 increased the overall cancer risk (OR 2.89; 95 % CI 2.47-3.38; p < .0001). Moreover, ovarian cancer grading remained in a relationship with both analysed polymorphisms; G1 tumours presented increased frequencies of hOGG1 Cys/Cys homozygotes (OR 18.33; 95 % CI 9.38-35.81; p < .0001) and XRCC1 Trp/Trp homozygotes (OR 20.50; 95 % CI 10.17-41.32; p < .0001). Furthermore, G1 ovarian cancers displayed an overrepresentation of Cys and Trp allele. In conclusion, hOGG1 Ser326Cys and XRCC1 Arg194Trp polymorphisms may be regarded as risk factors of ovarian cancer.
    No preview · Article · Jun 2015 · Tumor Biology
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    ABSTRACT: The XRCC2 gene plays a crucial role in double-strand DNA break repair by homologous recombination. Current literature provides clear evidence that XRCC2 polymorphisms may be associated with the development of certain types of cancer; however, still little is known about their association with endometrial cancer (EC). The single nucleotide polymorphism (SNP) -41657C/T (rs718282) of the XRCC2 gene was investigated by PCR-RFLP in 304 patients with EC and in 200 age- and sex-matched non-cancer controls. The analysis revealed a relationship between XRCC2 -41657C/T polymorphism and the incidence of EC. Endometrial cancer patients showed overrepresentation of the T allele of the SNP. The T/T homozygous variant increased the cancer risk. There were no significant differences between the distribution of XRCC2 -41657C/T genotypes in the subgroups according to histological grade. This is the first study that links the SNP -41657C/T (rs718282) of the XRCC2 gene with EC in Polish women. The results support the hypothesis that this polymorphism may be positively correlated with the incidence of EC.
    Full-text · Article · May 2015 · Polish journal of pathology: official journal of the Polish Society of Pathologists
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    ABSTRACT: Double strand DNA breaks are the most dangerous DNA damage which, if non-repaired or misrepaired, may result in genomic instability, cancer transformation or cell death. RAD51 and XRCC2 encode proteins that are important for the repair of double-strand DNA breaks by homologous recombination. Therefore, genetic variability in these genes may contribute to the occurrence and progression of triple-negative breast cancer. The polymorphisms of the XRCC2 gene -41657C/T (rs718282) and of the RAD51 gene, -172G/T (rs1801321), were investigated by PCR-RFLP in 70 patients with triple-negative breast cancer and 70 age- and sex matched non-cancer controls. The obtained results demonstrated a significant positive association between the RAD51 T/T genotype and TNBC, with an adjusted odds ratio (OR) of 4.94 (p = 0.001). The homozygous T/T genotype was found in 60 % of TNBC cases and in 14 % of the used controls. Variant 172 T allele of RAD51 increased cancer risk (OR = 2.81 (1.72-4.58), p < .0001). No significant associations were observed between -41657C/T genotype of XRCC2 and the incidence of TNBC. There were no significant differences between the distribution of XRCC2 -41657C/T genotypes in the subgroups assigned to histological grades. The obtained results indicate that the polymorphism of RAD51, but not of XRCC2 gene, may be positively associated with the incidence of triple-negative breast carcinoma in the population of Polish women.
    Preview · Article · Mar 2015 · Pathology & Oncology Research
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    ABSTRACT: Triple-negative breast cancer (TNBC) is characterised by worse clinical outcome and poor prognosis. The alterations in the oncogenes and tumor suppressor genes as well as microsatellite instability (MSI) have been associated with breast cancer development. It is knowledge that the most common mechanism inducing MSI in many cancer is genomic rearrangements found in the hMSH2 (human MutS homolog 2) gene. In this report we genotyped two polymorphisms of hMSH2 DNA repair gene in 70 TNBC patients and 70 age-matched cancer-free women using RFLP-PCR. The following polymorphisms were studied: an A/G transition at 127 positions producing an Asn/Ser substitution at codon 127 (the Asn127Ser polymorphism, rs17217772) and a G/A transition at 1032 position resulting in a Gly/Asp change at codon 322 (the Gly322Asp polymorphism, rs4987188). We found an association between the hMSH2 Asp/Asp and Gly/Asp genotypes and TNBC occurence. Variant Asp allele of hMSH2 decreased cancer risk [odds ratio (OR) 0.11; 95 % confidence interval (CI) 0.05-0.21]. The risk of TNBC in the carriers of the Gly322Gly-Asn127Ser combined genotype was increased (OR 3.71; 95 % CI 1.36-10.10). However the risk of TNBC was not alter by polymorphism Asn127Ser of the hMSH2 gene. The Gly322Asp polymorphism of the hMSH2 gene may be linked with TNBC occurrence in Polish women.
    Preview · Article · Aug 2014 · Familial Cancer
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    ABSTRACT: Purpose: Many of the studies have analyzed cell repair capabilities, following cancer development. The cellular reaction to DNA damaging agents can modulate the susceptibility to various tumors. This reaction is mainly determined by DNA repair efficacy which, in turn, may be influenced by the variability of DNA repair genes, expressed by their polymorphisms. Methods: This report describes studies of the distribution of genotypes and the frequency of alleles of the G135C (rs1801320) and G172T (rs1801321) RAD51 polymorphism in 630 paraffin-embedded samples of tumor tissue from patients with endometrial cancer. DNA from 630 normal endometrial tissues served as control. RAD51 polymorphisms were determined by PCR-RFLP. Results: In the present work, a relationship was identified between RAD51 G135C polymorphism and the incidence of endometrial cancer. Endometrial cancer patients had an overrepresentation of 135C allele. The 135C/C homozygous variant increased cancer risk. A tendency towards a decreased risk of endometrial cancer was observed with the occurrence of combined G135C-G172G genotype of RAD51 polymorphism. An association was confirmed between RAD51 G135C and G172T polymorphisms and endometrial cancer progression, assessed by the histological grades. Conclusions: The results support the hypothesis that RAD51 G135C and G172T polymorphisms may be associated with endometrial cancer occurrence and/or progression.
    Preview · Article · Jun 2014 · Archives of Gynecology and Obstetrics
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    ABSTRACT: XRCC2 and XRCC3 genes involved in homologous recombination repair (HRR) of DNA and in the maintenance of the genome integrity play a crucial role in protecting against mutations that lead to cancer. The aim of the present work was to evaluate associations between the risk of triple-negative breast cancer (TNBC) and polymorphisms in the genes, encoding for two key proteins of HRR: XRCC2 Arg188His (c. 563 G>A; rs3218536, Genbank Accession Number NT 007914) and XRCC3 Thr241Met (c. 722 C>T; rs861539, Genbank Accession Number NT 026437). The polymorphisms of the XRCC2 and XRCC3 were investigated by PCR-RFLP in 70 patients with TNBC and 70 age- and sex-matched non-cancer controls. In the present work, a relationship was identified between XRCC2 Arg188His polymorphism and the incidence of triple-negative breast cancer. The 188His allele and 188His/His homozygous variant increased cancer risk. An association was confirmed between XRCC2 Arg188His and XRCC3 Thr241Met polymorphisms and TNBC progression, assessed by the degree of lymph node metastases and histological grades. In conclusion, XRCC2 Arg188His and XRCC3 Thr241Met polymorphisms may be regarded as predictive factors of triple-negative breast cancer in female population.
    Full-text · Article · Apr 2014 · Clinical and Experimental Medicine
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    ABSTRACT: Triple-negative breast cancer (TNBC) refers to about 15-20 % of all breast cancer cases. It is characterized by worse clinical outcome, poor prognosis, and absence of prognostic indicators. Several polymorphisms in the nucleotide excision repair (NER) and base excision repair (BER) gene have been extensively studied in association with various human cancers. The aim of this study was to evaluate the role of the hOGG1-Ser326Cys (rs13181), XRCC1-Arg194Trp (rs1799782), and ERCC2-Lys751Gln (rs13181) gene polymorphisms with clinical parameters and the risk for development of triple-negative breast cancer. Our research included 70 patients with TNBC and 70 healthy controls. Gene polymorphisms were genotyped by the PCR-RFLP (restriction fragment length polymorphism) method. The genotype distributions were contrasted by the chi-square test, and the significance of the polymorphism was assessed by multiple logistic regression producing odds ratios (ORs) and 95 % confidence intervals (CIs). In the present work, a relationship was identified between ERCC2-Lys751Gln polymorphism and the incidence of triple-negative breast cancer. An association was observed between triple-negative breast carcinoma occurrence and the presence of Gln/Gln genotype (OR = 5.71 (2.12-5.43), p = 0.0007). A tendency for an increased risk of TNBC was detected with the occurrence of 751Gln allele of ERCC2 polymorphism. No significant associations between Ser326Cys and Arg194Trp genotype and TNBC were observed. We suggest that the Lys751Gln polymorphism of the ERCC2 gene may be risk factors for triple-negative breast cancer development in Polish women.
    Full-text · Article · Jan 2014 · Tumor Biology
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    ABSTRACT: Genetic polymorphisms in the RAD51 gene may be associated with increased cancer risk. The aim of the present study was to evaluate associations between the risk of ovarian cancer and 135G>C (rs1801320) and 172G>T (rs1801321) polymorphisms in the RAD51 gene. We analysed the distribution of genotypes and frequency of alleles of the RAD51 polymorphisms in 210 women with ovarian cancer and 210 healthy controls. Both polymorphisms were genotyped by restriction fragment length polymorphism-polymerase chain reaction (PCR-RFLP). In the present study only 135G>C polymorphism of the RAD51 gene was associated with ovarian cancer risk. The distribution of genotypes for 135G>C in ovarian cancer patients vs. controls was: 20% vs. 30% for G/G, 22% vs. 47% for G/C, and 58% vs. 23% for C/C genotype, respectively. We found evidence of an increased ovarian cancer risk in C/C homozygotes but not in heterozygotes. The 135C allele of RAD51 increased cancer risk. In the present work we demonstrated a significant positive association between the RAD51 135G>C polymorphism and ovarian carcinoma in Poland. However, this gene requires further understanding of its interaction with other genes involved in tumour development.
    No preview · Article · Dec 2013 · Polish journal of pathology: official journal of the Polish Society of Pathologists
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    ABSTRACT: Endometrial cancer belongs to the commonest malignancy in females after breast cancer, malignant neoplasm of female genitals in Europe and North America but there is still not significant improvement as far as the curability of this neoplasm is concerned, especially its advanced forms. That is why there is need to define new factors that could be not only diagnostic but also predictve factors. In present study we analyzed the mRNA PTEN expression by quantitative real-time polymerase chain reaction (Q-PCR) in 123 women of endometrial carcinoma and 14 women of control group. Moreover we assessed oestrogen (ER) and progesterone receptors (PgR) in all cases. We defined the correlation between expression of PTEN gene and receptors and between PTEN expression and maturity grade of cancer. Neoplasm advancement grade G1 was diagnosed in 82.11 % of patients (n = 101), G2 in 9.76 % of patients (n = 12) and G3 in 8.13 % of patients (n = 10). Presence of ER and PgR and decreased expression of PTEN gene was found in majority of patients with endometrial cancer (79.12 % and 59.34 % respectively) and the most numerous group was with weak expression of ER and strong expression of PgR. There was no statistically significant difference in gene expression depending on receptors expression nor maturity grade of cancer (p > 0.05). Evaluation of expression of PTEN gene may turn out to be a very useful tool aimed at qualifying patients for different therapies of endometrial cancer and at searching of new diagnostic and therapeutic methods of this cancer independently on its receptor status nor maturity grade of cancer.
    Full-text · Article · Sep 2013 · Pathology & Oncology Research

  • No preview · Article · Mar 2013 · Polish journal of pathology: official journal of the Polish Society of Pathologists
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    ABSTRACT: The prognostic value of the MDM2 gene amplification/expression in many types of cancer remains unclear. Polymorphisms in the promoter region of the MDM2 gene have been shown to alter the protein expression and thus, may play a role in carcinogenesis. The aim of the present study was to evaluate the association between the risk of endometrial cancer and SNP309 polymorphisms in the MDM2 gene. The genotype analysis of SNP309 MDM2 gene polymorphisms in 152 endometrial cancer patients and 100 controls of cancer-free subjects, in the Polish population, was performed using the PCR-based restriction fragment length polymorphism (PCR-RFLP). In the presented study, an association between MDM2 SNP309 polymorphisms and the incidence of endometrial cancer was identified. Our results obtained for the SNP309 polymorphisms of the MDM2 gene indicated that both the G/G genotype and the G allele are strongly associated with endometrial cancer. We did not observe any relationship between gene polymorphism and endometrial cancer progression assessed by FIGO grade. This is the first study linking single nucleotide polymorphisms of the MDM2 gene with endometrial cancer incidence in the population of Polish women. The results support the hypothesis that the SNP309 polymorphism of the MDM2 gene may be associated with the incidence of endometrial cancer in the female population.
    No preview · Article · Dec 2012 · Polish journal of pathology: official journal of the Polish Society of Pathologists
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    ABSTRACT: Endometriosis is a common gynaecological disease of unknown etiology. Angiogenesis appears to be one of the processes involved in its pathogenesis. Angiogenic factors VEGF level is increased in patients with endometriosis. Studies have shown that endometriosis maybe associated with VEGF single nucleotide polymorphism (SNP) polymorphisms. Results from studies that assayed VEGF polymorphism in endometriosis are reviewed. Data in the literature suggest that VEGF SNPs such as: -460C/T +405G/C and 936C/T seem to be a risk factor for endometriosis.
    No preview · Article · Mar 2012 · Polski merkuriusz lekarski: organ Polskiego Towarzystwa Lekarskiego
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    ABSTRACT: Cancer cells have accelerated metabolism and high glucose requirements. The up-regulation of specific glucose transporters may represent a key mechanism by which malignant cells may achieve increased glucose uptake to support the high rate of glycolysis. In present study we analyzed the mRNA and protein expression of GLUT1 and GLUT3 glucose transporters by quantitative real-time polymerase chain reaction (Q-PCR) and Western blotting technique in 76 cases of endometrial carcinoma and 70 cases of breast carcinoma. SLC2A1 and SLCA2A3 mRNAs expression was found, respectively in 100% and 97.4% samples of endometrial cancers and only in 50% and 40% samples of breast cancers. In endometrial cancers GLUT1 and GLUT3 protein expression was identified in 67.1% and 30.3% of cases. Analogously, in breast cancers in 48.7% and 21% of samples, respectively. The results showed that both endometrial and breast poorly differentiated tumors (grade 2 and 3) had significantly higher GLUT1 and GLUT3 expression than well-differentiated tumors (grade 1). Statistically significant association was found between SLCA2A3 mRNA expression and estrogen and progesterone receptors status in breast cancers. GLUT1 has been reported to be involved in the uptake of glucose by endometrial and breast carcinoma cells earlier and the present study determined that GLUT3 expression is also involved. GLUT1 and GLUT3 seem to be important markers in endometrial and breast tumors differentiation.
    Full-text · Article · Jan 2012 · Pathology & Oncology Research
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    ABSTRACT: O-GlcNAcylation is an abundant, dynamic, and inducible posttranslational modification in which single β-N-acetylglucosamine residues are attached by O-glycosidic linkage to serine or treonine residues. It is suggested that abnormally regulated O-GlcNAcylation may contribute to the pathology of cancer. Cycling of O-GlcNAc residues on intracellular proteins is controlled by two enzymes, O-GlcNAc transferease (OGT), which catalyses the addition of O-GlcNAc residues and nucleocytoplasmic β-N-acetylglucosaminidase (O-GlcNAcase; encoded by MGEA5 gene), an enzyme involved in the removal of O-GlcNAc. In this study, relationship between the mRNA expressions of genes coding O-GlcNAc cycling enzymes in breast ductal carcinomas and clinicopathological parameters were analyzed. The results showed that poorly differentiated tumors (grade II and III) had significantly higher OGT expression than grade I tumors. Contrary, MGEA5 transcript levels were significantly lower in grade II and III in comparison with grade I tumors. The Spearman rank correlation showed the expressions of OGT and MGEA5 in breast cancer was negatively correlated (r = -0.430, P = 0.0002). Lymph node metastasis status was significantly associated with decreased MGEA5 mRNA expression. This result suggests that elevation in O-GlcNAc modification of proteins may be implicated in breast tumor progression and metastasis.
    Full-text · Article · May 2011 · Clinical and Experimental Medicine
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    ABSTRACT: Background: Single nucleotide polymorphisms in the DNA repair genes have been extensively studied in association with various human cancers such as breast cancer. Material and methods: We investigated an association of polymorphisms in the DNA repair genes XRCC2-Arg188His and RAD51-135G/C with the breast cancer risk. Genotypes were analysed by PCR-RFLP assays in 80 patients with breast cancer and 80 controls. Results: The distribution of the genotypes of XRCC2 Arg188His in both controls and patients did not differ significantly (p > 0,05) from those predicted by the Hardy-Weinberg distribution. The C/C genotype of RAD51 increased the risk of breast cancer occurrence (OR 2.29; 95% PU (0.91-5.72), p = 0.04). Conclusion: G135C polymorphism of the RAD51 gene may be associated with the incidence of sporadic breast cancer in Polish women.
    No preview · Article · Feb 2011 · Menopausal Review
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    ABSTRACT: Background : Several polymorphisms in the DNA repair gene have been extensively studied in the association with various human cancers such as breast cancer. Material and methods : We investigated the association of polymorphisms in the DNA repair genes XRCC1-Arg399Gln, XRCC2-Arg188His and RAD51-135G/C with the breast cancer risk. Genotypes were determined by PCR-RFLP assays in 220 patients with breast cancer and 220 age-matched healthy controls. Results : Our results demonstrated a significant positive association between the XRCC1 399Gln/Gln homozygous genotype and breast carcinoma, with an adjusted odds ratio (OR) of 2.08 [1.08-3.98]. The 399Gln allele variant was also associated with type I breast cancer (OR = 1.41 [0.98-2.01], p = 0.034). The distributions of genotypes and alleles of the genes XRCC2 and RAD51 polymorphism were not significantly associated with the different stages of breast carcinoma (p > 0.05). Conclusion : These results suggest that 399Gln allele of XRCC1 Arg399Gln may be a risk factor for breast cancer in the Polish population.
    No preview · Article · Sep 2010 · Polish journal of pathology: official journal of the Polish Society of Pathologists
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    ABSTRACT: Background: Microsatellite instability (MSI) is due to defective DNA mismatch repair. Defects in DNA mismatch-repair (MMR) genes lead to replication errors revealed as instability in microsatellite markers. Studies have shown that breast cancer may be associated with mutations in mismatch repair genes, such as MSH2, MSH3, MSH4, MSH6, MLH1, MLH3, PMS1 and MUTYH. Aim: Results from studies that assayed MMR in sporadic breast cancer are reviewed. Conclusion: Several data suggest that microsatellite instability seems to be a risk factor for breast cancer in subjects belonging to HNPCC (hereditary non-polyposis colorectal cancer) families with high incidence of this cancer and sporadic breast cancer.
    No preview · Article · Apr 2010 · Menopausal Review